Several commonly used scoring systems (SOFA, SAPS II, LODS, and SIRS) are currently lacking large sample data to confirm the predictive value of 30-day mortality from sepsis, and their clinical net benefits of predicting mortality are still inconclusive. The baseline data, LODS score, SAPS II score, SIRS score, SOFA score, and 30-day prognosis of patients who met the diagnostic criteria of sepsis were retrieved from the Medical Information Mart for Intensive Care III (MIMIC-III) intensive care unit (ICU) database. Receiver operating characteristic (ROC) curves and comparisons between the areas under the ROC curves (AUC) were conducted. Decision curve analysis (DCA) was performed to determine the net benefits between the four scoring systems and 30-day mortality of sepsis. For all cases in the cohort study, the AUC of LODS, SAPS II, SIRS, SOFA were 0.733, 0.787, 0.597, and 0.688, respectively. The differences between the scoring systems were statistically significant (all P-values < 0.0001), and stratified analyses (the elderly and non-elderly) also showed the superiority of SAPS II among the four systems. According to the DCA, the net benefit ranges in descending order were SAPS II, LODS, SOFA, and SIRS. For stratified analyses of the elderly or non-elderly groups, the results also showed that SAPS II had the most net benefit. Among the four commonly used scoring systems, the SAPS II score has the highest predictive value for 30-day mortality from sepsis, which is better than LODS, SIRS, and SOFA. The results of the DCA curves show that using the SAPS II score to predict the 30-day mortality of intensive care patients with sepsis to guide clinical applications may obtain the highest net benefit.